Human Gene SH2D2A (uc001fqd.2)
  Description: Homo sapiens SH2 domain containing 2A (SH2D2A), transcript variant 2, mRNA.
RefSeq Summary (NM_003975): This gene encodes an adaptor protein thought to function in T-cell signal transduction. A related protein in mouse is responsible for the activation of lymphocyte-specific protein-tyrosine kinase and functions in downstream signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010].
Transcript (Including UTRs)
   Position: hg19 chr1:156,776,035-156,786,640 Size: 10,606 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg19 chr1:156,776,970-156,786,500 Size: 9,531 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:156,776,035-156,786,640)mRNA (may differ from genome)Protein (389 aa)
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WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: SH22A_HUMAN
DESCRIPTION: RecName: Full=SH2 domain-containing protein 2A; AltName: Full=SH2 domain-containing adapter protein; AltName: Full=T cell-specific adapter protein; Short=TSAd; AltName: Full=VEGF receptor-associated protein;
FUNCTION: Could be a T-cell-specific adapter protein involved in the control of T-cell activation. May play a role in the CD4-p56- LCK-dependent signal transduction pathway. Could also play an important role in normal and pathological angiogenesis. Could be an adapter protein that facilitates and regulates interaction of KDR with effector proteins important to endothelial cell survival and proliferation.
SUBUNIT: Interacts with KDR. Interacts with TXK and ITK (By similarity).
SUBCELLULAR LOCATION: Cytoplasm.
TISSUE SPECIFICITY: Expression limited to tissues of the immune system and, in particular, activated T-cells. Expressed in peripheral blood leukocytes, thymus and spleen. Much lower expression or undetectable, in brain, placenta, skeletal muscle, prostate, testis, ovary, small intestine, and colon. Expressed at low levels in unstimulated T-cells, but not expressed in normal resting or activated B-cells. According to PubMed:10692392, expression is not restricted to activated T-cells, but strongly expressed in blood cell lineages, the endothelium and other cell and tissue types, such as heart, lung, and liver.
INDUCTION: Rapidly induced after activation of T-cells. However, the gene continues to be expressed in long-term cultures of activated T-cells.
PTM: Phosphorylated on tyrosine residues.
SIMILARITY: Contains 1 SH2 domain.
SEQUENCE CAUTION: Sequence=AAC99298.1; Type=Erroneous initiation;

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): SH2D2A
CDC HuGE Published Literature: SH2D2A
Positive Disease Associations: multiple sclerosis , rheumatoid arthritis
Related Studies:
  1. multiple sclerosis
    Dai KZ 2001, The T cell regulator gene SH2D2A contributes to the genetic susceptibility of multiple sclerosis, Genes and immunity. 2001 Aug;2(5):263-8. [PubMed 11528519]
    Since the SH2D2A protein modulates T cell activation, this may be a mechanism for how short SH2D2A alleles confer susceptibility to develop MS.
  2. rheumatoid arthritis
    Smerdel, A. et al. 2004, Genetic association between juvenile rheumatoid arthritis and polymorphism in the SH2D2A gene., Genes and immunity. 2004 Jun;5(4):310-2. [PubMed 15129233]
    Our data indicate that the 'short' alleles of the SH2D2A promoter could contribute to the genetic susceptibility to JRA.

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 8.81 RPKM in Whole Blood
Total median expression: 51.21 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -44.40140-0.317 Picture PostScript Text
3' UTR -105.35334-0.315 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000980 - SH2

Pfam Domains:
PF00017 - SH2 domain

SCOP Domains:
55550 - SH2 domain

ModBase Predicted Comparative 3D Structure on Q9NP31
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005070 SH3/SH2 adaptor activity
GO:0005515 protein binding
GO:0017124 SH3 domain binding

Biological Process:
GO:0001525 angiogenesis
GO:0007165 signal transduction
GO:0007275 multicellular organism development
GO:0008283 cell proliferation
GO:0009967 positive regulation of signal transduction
GO:0030154 cell differentiation
GO:0048010 vascular endothelial growth factor receptor signaling pathway

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  AY763098 - Homo sapiens SH2 domain containing adapter protein 2 transcript variant 3 (SH2D2A) mRNA, complete cds, alternatively spliced.
AY763100 - Homo sapiens SH2 domain containing adpater protein 2 transcript variant 2 (SH2D2A) mRNA, complete cds, alternatively spliced.
AF051325 - Homo sapiens SH3 domain containing adaptor protein (SCAP) mRNA, complete cds.
AJ000553 - Homo sapiens mRNA for T lymphocyte specific adaptor protein (SH2D2A).
AY763099 - Homo sapiens SH2 domain containing adapter protein 2 transcript variant 4 (SH2D2A) mRNA, complete cds, alternatively spliced.
BC012107 - Homo sapiens SH2 domain protein 2A, mRNA (cDNA clone MGC:20097 IMAGE:4636736), complete cds.
AF097744 - Homo sapiens VEGF receptor-associated adaptor protein (VRAP) mRNA, complete cds.
JD296157 - Sequence 277181 from Patent EP1572962.
JD192914 - Sequence 173938 from Patent EP1572962.
JD192514 - Sequence 173538 from Patent EP1572962.
JD368183 - Sequence 349207 from Patent EP1572962.
JD361811 - Sequence 342835 from Patent EP1572962.
JD236759 - Sequence 217783 from Patent EP1572962.
JD070956 - Sequence 51980 from Patent EP1572962.
AK222737 - Homo sapiens mRNA for SH2 domain protein 2A variant, clone: DMC02833.
AK313706 - Homo sapiens cDNA, FLJ94299, highly similar to Homo sapiens SH2 domain protein 2A (SH2D2A), mRNA.
KJ897953 - Synthetic construct Homo sapiens clone ccsbBroadEn_07347 SH2D2A gene, encodes complete protein.
EU832614 - Synthetic construct Homo sapiens clone HAIB:100067643; DKFZo008A1031 SH2 domain protein 2A protein (SH2D2A) gene, encodes complete protein.
EU832686 - Synthetic construct Homo sapiens clone HAIB:100067715; DKFZo004A1032 SH2 domain protein 2A protein (SH2D2A) gene, encodes complete protein.
AB528908 - Synthetic construct DNA, clone: pF1KE0682, Homo sapiens SH2D2A gene for SH2 domain protein 2A, without stop codon, in Flexi system.
JD055775 - Sequence 36799 from Patent EP1572962.
JD050312 - Sequence 31336 from Patent EP1572962.
JD051265 - Sequence 32289 from Patent EP1572962.
JD408823 - Sequence 389847 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04370 - VEGF signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein Q9NP31 (Reactome details) participates in the following event(s):

R-HSA-4420143 p-6Y-VEGFR2 binds SH2D2A
R-HSA-4420140 SRC1-1 binds SH2D2A and is recruited to VEGFR2
R-HSA-4420206 Phosphorylation of SRC-1
R-HSA-5357432 AXL binds SRC-1
R-HSA-5357429 AXL autophosphorylates on Y772 and Y814
R-HSA-5357479 p-AXL binds PI3K
R-HSA-5218819 VEGFA dimer:p-6Y-VEGFR2 dimer:PI3K phosphorylates PIP2 to PIP3
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-194138 Signaling by VEGF
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: NM_003975, NP_001154915, O43817, Q5VZS5, Q9NP31, Q9UPA7, SCAP, SH22A_HUMAN, TSAD, VRAP
UCSC ID: uc001fqd.2
RefSeq Accession: NM_003975
Protein: Q9NP31 (aka SH22A_HUMAN or SH2A_HUMAN)
CCDS: CCDS1159.1, CCDS53380.1, CCDS53381.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_003975.3
exon count: 9CDS single in 3' UTR: no RNA size: 1661
ORF size: 1170CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2525.00frame shift in genome: no % Coverage: 98.98
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.